The goal of this proposal is the identification of a specific molecular imaging probe that can noninvasively identify high risk atherosclerotic plaques in patients. Two key hallmarks of plaque at high risk for rupture are intraplaque hemorrhage and evidence of prior rupture. The protein fibrin is strongly associated with both hemorrhage and rupture, suggesting that fibrin is a highly specific marker of high risk plaque. On the other hand, fibrin is not present in earlier stages of plaque development, suggesting that fibrin imaging would be sensitive for high risk plaque versus stable/early disease. We hypothesize that the presence of fibrin in the coronary arteries is a predictive marker of the vulnerable plaque. We will develop a fibrin-specific fluorine-18 (F-18) labeled peptide for the ultimate purpose of identifying high risk plaque in at risk patients. In Phase I of the proposal we will prepare a series of fluorine derivatized peptides based on the known fibrin-binding peptide used in the MR probe EP-2104R and screen them with respect to fibrin affinity, fibrin specificity, and metabolic stability, and develop radiolabeling conditions for incorporation of F-18.